Abstract
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Nature Genetics |
| Vol/bind | 56 |
| Udgave nummer | 5 |
| Sider (fra-til) | 792-808 |
| Antal sider | 17 |
| ISSN | 1061-4036 |
| DOI | |
| Status | Udgivet - 2024 |
Bibliografisk note
Funding Information:Major financial support for the PTSD-PGC was provided by the National Institute of Mental Health (NIMH; R01MH106595 (to K.C.K., C.M.N., K.J.R. and M.B.S.), R01MH124847 (to C.M.N.) and R01MH124851 (to A.D.B., L.K.D. and K.C.K.)), the Stanley Center for Psychiatric Research at the Broad Institute and Cohen Veterans Bioscience. Statistical analyses were carried out on the NL Genetic Cluster computer (URL) hosted by SURFsara. Genotyping of samples was supported in part through the Stanley Center for Psychiatric Genetics at the Broad Institute of MIT and Harvard. This research has been conducted using the UKB resource under application 41209. This work would not have been possible without the contributions of the investigators who comprise the PGC-PTSD working group, and especially the more than 1,307,247 research participants worldwide who shared their life experiences and biological samples with PGC-PTSD investigators. We thank A.E. Aiello, B. Bradley, A. Gautam, R. Hammamieh, M. Jett, M.J. Lyons, D. Maurer, M.R. Mavissakalian and the late C.R. Erbes and R.E. McGlinchey for their contributions to this study.
Publisher Copyright:
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.
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Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder. / Nievergelt, Caroline M.; Maihofer, Adam X.; Atkinson, Elizabeth G.; Chen, Chia-Yen; Choi, Karmel W.; Coleman, Jonathan R. I.; Daskalakis, Nikolaos P.; Duncan, Laramie E.; Polimanti, Renato; Aaronson, Cindy; Amstadter, Ananda B.; Andersen, Soren B.; Andreassen, Ole A.; Arbisi, Paul A.; Ashley-Koch, Allison E.; Austin, S. Bryn; Avdibegoviç, Esmina; Babić, Dragan; Bacanu, Silviu Alin; Baker, Dewleen G.; Batzler, Anthony; Beckham, Jean C.; Belangero, Sintia; Benjet, Corina; Bergner, Carisa; Bierer, Linda M.; Biernacka, Joanna M.; Bierut, Laura J.; Bisson, Jonathan I.; Boks, Marco P.; Bolger, Elizabeth A.; Brandolino, Amber; Breen, Gerome; Bressan, Rodrigo Affonseca; Bryant, Richard A.; Bustamante, Angela C.; Bybjerg-Grauholm, Jonas; Bækvad-Hansen, Marie; Børglum, Anders D.; Børte, Sigrid; Cahn, Leah; Calabrese, Joseph R.; Caldas-de-Almeida, Jose Miguel; Chatzinakos, Chris; Cheema, Sheraz; Clouston, Sean A.P.; Colodro-Conde, Lucía; Coombes, Brandon J.; Cruz-Fuentes, Carlos S.; Dale, Anders M.; Dalvie, Shareefa; Davis, Lea K.; Deckert, Jürgen; Delahanty, Douglas L.; Dennis, Michelle F.; Desarnaud, Frank; DiPietro, Christopher P.; Disner, Seth G.; Docherty, Anna R.; Domschke, Katharina; Dyb, Grete; Kulenović, Alma Džubur; Edenberg, Howard J.; Evans, Alexandra; Fabbri, Chiara; Fani, Negar; Farrer, Lindsay A.; Feder, Adriana; Feeny, Norah C.; Flory, Janine D.; Forbes, David; Franz, Carol E.; Galea, Sandro; Garrett, Melanie E.; Gelaye, Bizu; Gelernter, Joel; Geuze, Elbert; Gillespie, Charles F.; Goleva, Slavina B.; Gordon, Scott D.; Goçi, Aferdita; Grasser, Lana Ruvolo; Guindalini, Camila; Haas, Magali; Hagenaars, Saskia; Hauser, Michael A.; Heath, Andrew C.; Hemmings, Sian M. J.; Hesselbrock, Victor; Hickie, Ian B.; Hogan, Kelleigh; Hougaard, David Michael; Huang, Hailiang; Huckins, Laura M.; Hveem, Kristian; Jakovljević, Miro; Javanbakht, Arash; Jenkins, Gregory D.; Johnson, Jessica; Jones, Ian; Jovanovic, Tanja; Karstoft, Karen-Inge; Kaufman, Milissa L.; Kennedy, James L.; Kessler, Ronald C.; Khan, Alaptagin; Kimbrel, Nathan A.; King, Anthony P.; Koen, Nastassja; Kotov, Roman; Kranzler, Henry R.; Krebs, Kristi; Kremen, William S.; Kuan, Pei-Fen; Lawford, Bruce R.; Lebois, Lauren A. M.; Lehto, Kelli; Levey, Daniel F.; Lewis, Catrin; Liberzon, Israel; Linnstaedt, Sarah D.; Logue, Mark W.; Lori, Adriana; Lu, Yi; Luft, Benjamin J.; Lupton, Michelle K.; Luykx, Jurjen J.; Makotkine, Iouri; Maples-Keller, Jessica L.; Marchese, Shelby; Marmar, Charles; Martin, Nicholas G.; Martínez-Levy, Gabriela A.; McAloney, Kerrie; McFarlane, Alexander; McLaughlin, Katie A.; McLean, Samuel A.; Medland, Sarah E.; Mehta, Divya; Meyers, Jacquelyn; Michopoulos, Vasiliki; Mikita, Elizabeth A.; Milani, Lili; Milberg, William; Miller, Mark W.; Morey, Rajendra A.; Morris, Charles Phillip; Mors, Ole; Mortensen, Preben Bo; Mufford, Mary S.; Nelson, Elliot C.; Nordentoft, Merete; Norman, Sonya B.; Nugent, Nicole R.; O’Donnell, Meaghan; Orcutt, Holly K.; Pan, Pedro M.; Panizzon, Matthew S.; Pathak, Gita A.; Peters, Edward S.; Peterson, Alan L.; Peverill, Matthew; Pietrzak, Robert H.; Polusny, Melissa A.; Porjesz, Bernice; Powers, Abigail; Qin, Xue-Jun; Ratanatharathorn, Andrew; Risbrough, Victoria B.; Roberts, Andrea L.; Rothbaum, Alex O.; Rothbaum, Barbara O.; Roy-Byrne, Peter; Ruggiero, Kenneth J.; Rung, Ariane; Runz, Heiko; Rutten, Bart P.F.; de Viteri, Stacey Saenz; Salum, Giovanni Abrahão; Sampson, Laura; Sanchez, Sixto E.; Santoro, Marcos; Seah, Carina; Seedat, Soraya; Seng, Julia S.; Shabalin, Andrey; Sheerin, Christina M.; Silove, Derrick; Smith, Alicia K.; Smoller, Jordan W.; Sponheim, Scott R.; Stein, Dan J.; Stensland, Synne; Stevens, Jennifer S.; Sumner, Jennifer A.; Teicher, Martin H.; Thompson, Wesley K.; Tiwari, Arun K.; Trapido, Edward; Uddin, Monica; Ursano, Robert J.; Valdimarsdóttir, Unnur; Van Hooff, Miranda; Vermetten, Eric; Vinkers, Christiaan H.; Voisey, Joanne; Wang, Yunpeng; Wang, Zhewu; Waszczuk, Monika; Weber, Heike; Wendt, Frank R.; Werge, Thomas; Williams, Michelle A.; Williamson, Douglas E.; Winsvold, Bendik S.; Winternitz, Sherry; Wolf, Christiane; Wolf, Erika J.; Xia, Yan; Xiong, Ying; Yehuda, Rachel; Young, Keith A.; Young, Ross McD.; Zai, Clement C.; Zai, Gwyneth C.; Zervas, Mark; Zhao, Hongyu; Zoellner, Lori A.; Zwart, John-Anker; deRoon-Cassini, Terri; van Rooij, Sanne J.H.; van den Heuvel, Leigh L.; Stein, Murray B.; Ressler, Kerry J.; Koenen, Karestan C.
I: Nature Genetics, Bind 56, Nr. 5, 2024, s. 792-808.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review
}
TY - JOUR
T1 - Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder
AU - Nievergelt, Caroline M.
AU - Maihofer, Adam X.
AU - Atkinson, Elizabeth G.
AU - Chen, Chia-Yen
AU - Choi, Karmel W.
AU - Coleman, Jonathan R. I.
AU - Daskalakis, Nikolaos P.
AU - Duncan, Laramie E.
AU - Polimanti, Renato
AU - Aaronson, Cindy
AU - Amstadter, Ananda B.
AU - Andersen, Soren B.
AU - Andreassen, Ole A.
AU - Arbisi, Paul A.
AU - Ashley-Koch, Allison E.
AU - Austin, S. Bryn
AU - Avdibegoviç, Esmina
AU - Babić, Dragan
AU - Bacanu, Silviu Alin
AU - Baker, Dewleen G.
AU - Batzler, Anthony
AU - Beckham, Jean C.
AU - Belangero, Sintia
AU - Benjet, Corina
AU - Bergner, Carisa
AU - Bierer, Linda M.
AU - Biernacka, Joanna M.
AU - Bierut, Laura J.
AU - Bisson, Jonathan I.
AU - Boks, Marco P.
AU - Bolger, Elizabeth A.
AU - Brandolino, Amber
AU - Breen, Gerome
AU - Bressan, Rodrigo Affonseca
AU - Bryant, Richard A.
AU - Bustamante, Angela C.
AU - Bybjerg-Grauholm, Jonas
AU - Bækvad-Hansen, Marie
AU - Børglum, Anders D.
AU - Børte, Sigrid
AU - Cahn, Leah
AU - Calabrese, Joseph R.
AU - Caldas-de-Almeida, Jose Miguel
AU - Chatzinakos, Chris
AU - Cheema, Sheraz
AU - Clouston, Sean A.P.
AU - Colodro-Conde, Lucía
AU - Coombes, Brandon J.
AU - Cruz-Fuentes, Carlos S.
AU - Dale, Anders M.
AU - Dalvie, Shareefa
AU - Davis, Lea K.
AU - Deckert, Jürgen
AU - Delahanty, Douglas L.
AU - Dennis, Michelle F.
AU - Desarnaud, Frank
AU - DiPietro, Christopher P.
AU - Disner, Seth G.
AU - Docherty, Anna R.
AU - Domschke, Katharina
AU - Dyb, Grete
AU - Kulenović, Alma Džubur
AU - Edenberg, Howard J.
AU - Evans, Alexandra
AU - Fabbri, Chiara
AU - Fani, Negar
AU - Farrer, Lindsay A.
AU - Feder, Adriana
AU - Feeny, Norah C.
AU - Flory, Janine D.
AU - Forbes, David
AU - Franz, Carol E.
AU - Galea, Sandro
AU - Garrett, Melanie E.
AU - Gelaye, Bizu
AU - Gelernter, Joel
AU - Geuze, Elbert
AU - Gillespie, Charles F.
AU - Goleva, Slavina B.
AU - Gordon, Scott D.
AU - Goçi, Aferdita
AU - Grasser, Lana Ruvolo
AU - Guindalini, Camila
AU - Haas, Magali
AU - Hagenaars, Saskia
AU - Hauser, Michael A.
AU - Heath, Andrew C.
AU - Hemmings, Sian M. J.
AU - Hesselbrock, Victor
AU - Hickie, Ian B.
AU - Hogan, Kelleigh
AU - Hougaard, David Michael
AU - Huang, Hailiang
AU - Huckins, Laura M.
AU - Hveem, Kristian
AU - Jakovljević, Miro
AU - Javanbakht, Arash
AU - Jenkins, Gregory D.
AU - Johnson, Jessica
AU - Jones, Ian
AU - Jovanovic, Tanja
AU - Karstoft, Karen-Inge
AU - Kaufman, Milissa L.
AU - Kennedy, James L.
AU - Kessler, Ronald C.
AU - Khan, Alaptagin
AU - Kimbrel, Nathan A.
AU - King, Anthony P.
AU - Koen, Nastassja
AU - Kotov, Roman
AU - Kranzler, Henry R.
AU - Krebs, Kristi
AU - Kremen, William S.
AU - Kuan, Pei-Fen
AU - Lawford, Bruce R.
AU - Lebois, Lauren A. M.
AU - Lehto, Kelli
AU - Levey, Daniel F.
AU - Lewis, Catrin
AU - Liberzon, Israel
AU - Linnstaedt, Sarah D.
AU - Logue, Mark W.
AU - Lori, Adriana
AU - Lu, Yi
AU - Luft, Benjamin J.
AU - Lupton, Michelle K.
AU - Luykx, Jurjen J.
AU - Makotkine, Iouri
AU - Maples-Keller, Jessica L.
AU - Marchese, Shelby
AU - Marmar, Charles
AU - Martin, Nicholas G.
AU - Martínez-Levy, Gabriela A.
AU - McAloney, Kerrie
AU - McFarlane, Alexander
AU - McLaughlin, Katie A.
AU - McLean, Samuel A.
AU - Medland, Sarah E.
AU - Mehta, Divya
AU - Meyers, Jacquelyn
AU - Michopoulos, Vasiliki
AU - Mikita, Elizabeth A.
AU - Milani, Lili
AU - Milberg, William
AU - Miller, Mark W.
AU - Morey, Rajendra A.
AU - Morris, Charles Phillip
AU - Mors, Ole
AU - Mortensen, Preben Bo
AU - Mufford, Mary S.
AU - Nelson, Elliot C.
AU - Nordentoft, Merete
AU - Norman, Sonya B.
AU - Nugent, Nicole R.
AU - O’Donnell, Meaghan
AU - Orcutt, Holly K.
AU - Pan, Pedro M.
AU - Panizzon, Matthew S.
AU - Pathak, Gita A.
AU - Peters, Edward S.
AU - Peterson, Alan L.
AU - Peverill, Matthew
AU - Pietrzak, Robert H.
AU - Polusny, Melissa A.
AU - Porjesz, Bernice
AU - Powers, Abigail
AU - Qin, Xue-Jun
AU - Ratanatharathorn, Andrew
AU - Risbrough, Victoria B.
AU - Roberts, Andrea L.
AU - Rothbaum, Alex O.
AU - Rothbaum, Barbara O.
AU - Roy-Byrne, Peter
AU - Ruggiero, Kenneth J.
AU - Rung, Ariane
AU - Runz, Heiko
AU - Rutten, Bart P.F.
AU - de Viteri, Stacey Saenz
AU - Salum, Giovanni Abrahão
AU - Sampson, Laura
AU - Sanchez, Sixto E.
AU - Santoro, Marcos
AU - Seah, Carina
AU - Seedat, Soraya
AU - Seng, Julia S.
AU - Shabalin, Andrey
AU - Sheerin, Christina M.
AU - Silove, Derrick
AU - Smith, Alicia K.
AU - Smoller, Jordan W.
AU - Sponheim, Scott R.
AU - Stein, Dan J.
AU - Stensland, Synne
AU - Stevens, Jennifer S.
AU - Sumner, Jennifer A.
AU - Teicher, Martin H.
AU - Thompson, Wesley K.
AU - Tiwari, Arun K.
AU - Trapido, Edward
AU - Uddin, Monica
AU - Ursano, Robert J.
AU - Valdimarsdóttir, Unnur
AU - Van Hooff, Miranda
AU - Vermetten, Eric
AU - Vinkers, Christiaan H.
AU - Voisey, Joanne
AU - Wang, Yunpeng
AU - Wang, Zhewu
AU - Waszczuk, Monika
AU - Weber, Heike
AU - Wendt, Frank R.
AU - Werge, Thomas
AU - Williams, Michelle A.
AU - Williamson, Douglas E.
AU - Winsvold, Bendik S.
AU - Winternitz, Sherry
AU - Wolf, Christiane
AU - Wolf, Erika J.
AU - Xia, Yan
AU - Xiong, Ying
AU - Yehuda, Rachel
AU - Young, Keith A.
AU - Young, Ross McD.
AU - Zai, Clement C.
AU - Zai, Gwyneth C.
AU - Zervas, Mark
AU - Zhao, Hongyu
AU - Zoellner, Lori A.
AU - Zwart, John-Anker
AU - deRoon-Cassini, Terri
AU - van Rooij, Sanne J.H.
AU - van den Heuvel, Leigh L.
AU - Stein, Murray B.
AU - Ressler, Kerry J.
AU - Koenen, Karestan C.
N1 - Publisher Copyright: © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024.
PY - 2024
Y1 - 2024
N2 - Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.
AB - Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.
U2 - 10.1038/s41588-024-01707-9
DO - 10.1038/s41588-024-01707-9
M3 - Journal article
C2 - 38637617
AN - SCOPUS:85190650468
VL - 56
SP - 792
EP - 808
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 5
ER -